Resumen

Introduction. The present study aimed to elucidate the potential antifibrotic effects of pinocembrin (PIN), a flavanone found abundantly in honey and propolis, by studying its effect on different oxidative stress, inflammatory and fibrosis markers in an experimental model of CCl₄-induced liver fibrosis. Material and methods. PIN (20 mg/kg) was given orally 3 times/week for 6 consecutive weeks alternating with CCl₄ (0.5 mL/kg, 1:1 mixture with corn oil, i. p.) twice weekly. Different hepatotoxicity indices, oxidative stress, inflammatory and liver fibrosis markers were assessed. Results. PIN significantly restored liver transaminases and total cholesterol to normal levels. Also, PIN ameliorated oxidative stress injury evoked by CCl₄ as evidenced by inhibition of reduced glutathione depletion and lipid peroxidation as well as elevation of antioxidant enzyme superoxide dismutase (SOD). Further, PIN upregulated the nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), thereby inducing the expression and activity of the cytoprotective enzyme hemeoxygenase-1 (HO-1). Moreover, PIN alleviated pro-inflammatory cytokines such as TNF-á via inhibiting nuclear factor-êB (NF-êB) activation. As markers of fibrosis, collagen and á-SMA expression increased markedly in the CCl₄ group and PIN prevented these alterations. In addition, PIN down-regulated TGFâ1 and p-Smad2/3, thereby inhibiting TGFâ1/Smad signaling pathway. Conclusion. These results suggest that PIN possess potent antifibrotic effects that can be explained on its antioxidant properties. It ameliorates oxidative stress and inflammation during induction of fibrogenesis via its ability to augment cellular antioxidant defenses, activating Nrf2-mediated HO-1 expression and modulating NF-êB and TGF-â1/Smad signaling pathway.

Palabras clave: Pinocembrin CCl₄ NF-êB Nrf2 HO-1.

2018-08-20   |   139 visitas   |   Evalua este artículo 0 valoraciones

Vol. 17 Núm.2. Marzo-Abril 2018 Pags. 298-308 Ann Hepatol 2018; 17(2)